Abstract
Thiamine (vitamin B1) has a key role in protection against renal disease by providing the thiamine pyrophosphate cofactor for transketolase and thereby maintaining oxidative and reductive pentosephosphate pathway activities key in countering oxidative and metabolic stress. The link to renal disease is amplified by increased washout and deficiency in renal disease, which in diabetic nephropathy may be linked to tissue-specific downregulation of thiamine transporters. Transketolase is part of the antistress gene response coordinated by transcription factor NF-E2–related factor-2 (nrf2) and activated by dietary bioactive and synthetic activators. Such activators have been found to be beneficial in the treatment of diabetic nephropathy wherein increased transketolase activity may have a key role. High dose thiamine supplements prevented the development of nephropathy in experimental diabetes and in a recent pilot scale trial reversed early stage nephropathy in patients with type 2 diabetes. Transketolase gene TKT variability and increased fractional excretion of thiamine were linked to susceptibility and progression of diabetic nephropathy. A definitive, large-scale trial of thiamine supplements for treatment of early stage diabetic nephropathy is now desirable.
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Brady JA, Rock CL, Horneffer MR. Thiamin status, diuretic medications, and the management of congestive heart failures. J Am Diet Assoc 1995; 95: 541–544.
Thornalley PJ, Babaei-Jadidi R, Al Ali H et al. High prevalence of low plasma thiamine concentration in diabetes linked to marker of vascular disease. Diabetologia 2007; 50: 2164–2170.
Soh Y, Song BJ, Jeng JJ et al. Critical role of Arg(433) in rat transketolase activity as probed by site-directed mutagenesis. Biochem J 1998; 333: 367–372.
Finglas PM. Thiamin. Int J Vitam Nutr Res 1993; 63: 270–274.
Tasevska N, Runswick SA, McTaggart A et al. Twenty-four-hour urinary thiamine as a biomarker for the assessment of thiamine intake. Eur J Clin Nutr 2007; 62: 1139–1147.
European Food Safety Authority. Scientific Opinion of the Panel on Food Additives and Nutrient Sources added to Food (ANS) on a request from the Commission on Benfotiamine, thiamine monophosphate chloride and thiamine pyrophosphate chloride, as sources of vitamin B1. EFSA J 2008; 864: 1–31.
Rabbani N, Shahzad Alam S, Riaz S et al. High dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a pilot randomised, double-blind, placebo-controlled study. Diabetologia 2008; 52: 208–212.
Wang AYM, Sea MMM, Ip R et al. Independent effects of residual renal function and dialysis adequacy on dietary micronutrient intakes in patients receiving continuous ambulatory peritoneal dialysis. Am J Clin Nutr 2002; 76: 569–576.
Heaf J, Jakobsen U, Tvedegaard E et al. Dietary habits and nutritional status of renal transplant patients. J Renal Nutr 2004; 14: 20–25.
Hung SC, Hung SH, Tarng DC et al. Thiamine deficiency and unexplained encephalopathy in hemodialysis and peritoneal dialysis patients. Am J Kidney Dis 2001; 38: 941–947.
Dutta B, Huang W, Molero M et al. Cloning of the human thiamine transporter, a member of the folate transporter family. J Biol Chem 1999; 274: 31925–31929.
Rajgopal A, Edmondnson A, Goldman ID et al. SLC19A3 encodes a second thiamine transporter ThTr2. Biochim Biophys Acta Mol Basis Dis 2001; 1537: 175–178.
Matherly LH. Molecular and cellular biology of the human reduced folate carrier. Prog Nucleic Acid Res Mol Biol 2001; 67: 131–162.
Zhao R, Gao F, Goldman ID. Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells. Am J Physiol Cell Physiol 2002; 282: C1512–C1517.
Zhao RB, Gao F, Wang YH et al. Impact of the reduced folate carrier on the accumulation of active thiamin metabolites in murine leukemia cells. J Biol Chem 2001; 276: 1114–1118.
Lindhurst MJ, Fiermonte G, Song S et al. Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia. PNAS 2006; 103: 15927–15932.
Kang J, Samuels DC. The evidence that the DNC (SLC25A19) is not the mitochondrial deoxyribonucleotide carrier. Mitochondrion 2008; 8: 103–108.
Said HM, Balamurugan K, Subramanian VS et al. Expression and functional contribution of hTHTR-2 in thiamin absorption in human intestine. Am J Physiol Gastrointest Liver Physiol 2004; 286: G491–G498.
Reidling JC, Subramanian VS, Dudeja PK et al. Expression and promoter analysis of SLC19A2 in the human intestine. Biochim Biophys Acta 2002; 1561: 180–187.
Eudy JD, Spiegelstein O, Barber RC et al. Identification and characterization of the human and mouse SLC19A3 gene: A novel member of the reduced folate family of micronutrient transporter genes. Mol Genet Metab 2000; 71: 581–590.
Trippett TM, Garcia S, Manova K et al. Localization of a human reduced folate carrier protein in the mitochondrial as well as the cell membrane of leukemia cells. Cancer Res 2001; 61: 1941–1947.
Babaei-Jadidi R, Karachalias N, Kupich C et al. High dose thiamine therapy counters dyslipidaemia in streptozotocin-induced diabetic rats. Diabetologia 2004; 47: 2235–2246.
Chin E, Zhou J, Bondy C. Anatomical and developmental patterns of facilitative glucose transporter gene-expression in the rat kidney. J Clin Invest 1993; 91: 1810–1815.
Tallaksen CME, Bohmer T, Karlsen J et al. Determination of thiamin and its phosphate esters in human blood, plasma, and urine. Vitam Coenzymes 1997; 279 (Pt I): 67–74.
Dolce V, Fiermonte G, Runswick MJ et al. The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals. Proc Natl Acad Sci USA 2001; 98: 2284–2288.
Gastaldi G, Coya E, Verri A et al. Transport of thiamin in rat renal brush border membrane vesicles. Kidney Int 2002; 57: 2043–2054.
Morshed KM, Ross DM, McMartin KE. Folate transport proteins mediate the bidirectional transport of 5-methyltetrahydrofolate in cultured human proximal tubule cells. J Nutr 1997; 127: 1137–1147.
Rindi G, Laforenza U. Thiamine intestinal transport and related issues: recent aspects. PSEBM 2000; 224: 246–255.
Balamurugan K, Said HM. Functional role of specific amino acid residues in human thiamine transporter SLC19A2: mutational analysis. Am J Physiol Gastrointest Liver Physiol 2002; 283: G37–G43.
Fleming JC, Tartaglini E, Steinkamp MP et al. The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter. Nat Genet 1999; 22: 305–308.
Diaz GA, Banikazemi M, Oishi K et al. Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome. Nat Genet 1999; 22: 309–312.
Labay V, Raz T, Baron D et al. Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness. Nat Genet 1999; 22: 300–304.
Rosenberg MJ, Agarwala R, Bouffard G et al. Mutant deoxynucleotide carrier is associated with congenital microcephaly. Nat Genet 2002; 32: 175–179.
Larkin JR, Thornalley PJ. High glucose causes a decrease in expression of thiamine transporters in human proximal tubule epithelial cells in vitro. Diabetologia 2008; 51: 219.
Patrini C, Laforenza U, Gastaldi G et al. Effects of insulin on thiamine intestinal transport in rat everted jejunal sacs. J Physiol (London) 1996; 493: 100S–101S.
Babaei-Jadidi R, Karachalias N, Ahmed N et al. Prevention of incipient diabetic nephropathy by high dose thiamine and Benfotiamine. Diabetes 2003; 52: 2110–2120.
Naggar H, Ola MS, Moore P et al. Downregulation of reduced-folate transporter by glucose in cultured RPE cells and in RPE of diabetic mice. Invest Ophthalmol Vis Sci 2002; 43: 556–563.
Laforenza U, Patrini C, Alvisi C et al. Thiamine uptake in human intestinal biopsy specimens, including observations from a patient with acute thiamine deficiency. Am J Clin Nutr 1997; 66: 320–326.
AntonySunil A, Babaei-Jadidi R, Rabbani N et al. Increased thiamine transporter contents of red blood cells and peripheral blood mononuclear leukocytes in type 1 and type 2 diabetic patients. Diabetes 2007; 56: A609.
Halwachs S, Kneuer C, Honscha W. Downregulation of the reduced folate carrier transport activity by phenobarbital-type cytochrome P450 inducers and protein kinase C activators. Biochim Biophys Acta 2007; 1768: 1671–1679.
Heinz J, Domrose U, Westphal S et al. Washout of water-soluble vitamins and of homocysteine during haemodialysis: effect of high-flux and low-flux dialyser membranes. Nephrology 2008; 13: 384–389.
Chychul LM, Basu TK, Dasgupta MK. Continuous ambulatory peritoneal dialysis and micronutrients: a review. Nutr Res 1991; 11: 513–525.
Cheng JZ, Yang YS, Singh SP et al. Two distinct 4-hydroxynonenal metabolizing glutathione S-transferase isozymes are differentially expressed in human tissues. Biochem Biophys Res Commun 2001; 282: 1268–1274.
Xue M, Qian Q, Adaikalakoteswari A et al. Activation of NF-E2-related factor-2 reverses biochemical dysfunction of endothelial cells induced by hyperglycemia linked to vascular disease. Diabetes 2008; 57: 2809–2817.
Thornalley PJ, Qian Q, Rabbani N. Prevention of dicarbonyl stress induced by hyperglycaemia in microvascular endothelial cells by sulforaphane. Diabetologia 2008; 51: 1301.
Thornalley PJ. The potential role of thiamine (vitamin B1) in diabetic complications. Curr Diabetes Res 2005; 1: 287–298.
Terbukhina RV, Ostrovsky YM, Petushok VG et al. Effect of thiamine deprivation on thiamine metabolism in mice. J Nutr 1981; 111: 505–513.
Thimmulappa RK, Mai KH, Srisuma S et al. Identification of nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide array. Cancer Res 2002; 62: 5196–5203.
Kwak MK, Wakabayashi N, Itoh K et al. Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival. J Biol Chem 2003; 278: 8135–8145.
Thornalley PJ, IARC Workgroup. Cruciferous vegetables, isothiocyanates and indoles. IARC handbook on chemoprevention of cancer. Lyon: IARC Press, 2004.
Maiyoh GK, Kuh JE, Casaschi A et al. Cruciferous indole-3-carbinol inhibits apolipoprotein B secretion in HepG2 cells. J Nutr 2007; 137: 2185–2189.
Chen C, Pung D, Leong V et al. Induction of detoxifying enzymes by garlic organosulfur compounds through transcription factor nrf2: effect of chemical structure and stress signals. Free Radic Biol Med 2004; 37: 1578–1590.
Tanigawa S, Fujii M, Hou DX. Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Free Radic Biol Med 2007; 42: 1690–1703.
Mann GE, Rowlands DJ, Li FYL et al. Activation of endothelial nitric oxide synthase by dietary isoflavones: role of NO in nrf2-mediated antioxidant gene expression. Cardiovasc Res 2007; 75: 261–274.
Ben Dor A, Steiner M, Gheber L et al. Carotenoids activate the antioxidant response element transcription system. Mol Cancer Ther 2005; 4: 177–186.
Gao L, Wang JK, Sekhar KR et al. Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. J Biol Chem 2007; 282: 2529–2537.
Yates MS, Tauchi M, Katsuoka F et al. Pharmacodynamic characterization of chemopreventive triterpenoids as exceptionally potent inducers of Nrf2-regulated genes. Mol Cancer Ther 2007; 6: 154–162.
Fukuchi Y, Kato Y, Okunishi I et al. 6-Methylsulfinylhexyl isothiocyanate, an antioxidant derived from Wasabia japonica MATUM, ameliorates diabetic nephropathy in type 2 diabetic mice. Food Sci Technol Res 2004; 10: 290–295.
Sharma S, Anjaneyulu M, Kulkarni SK et al. Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats. Pharmacology 2006; 76: 69–75.
Anjaneyulu M, Chopra K. Quercetin, an anti-oxidant bioflavonoid, attenuates diabetic nephropathy in rats. Clin Exp Pharmacol Physiol 2004; 31: 244–248.
Schwartz SL, Denham DS, Hurwitz CA et al. Bardoxolone methyl shown to improve renal function in patients with chronic kidney disease and type 2 diabetes mellitus. Diabetes 2009; 58: A30.
Rabbani N, Alam S, Riaz S et al. Thiamine in diabetic nephropathy: a novel treatment modality? Reply to Alkhalaf A, Kleefstra N, Groenier KH et al. [letter]. Diabetologia 2009; 52: 1214–1216.
AntonySunil A, Perkins B, Krolewski A et al. Thiamine status and risk of early renal function decline in type 1 diabetic patients. Diabetologia 2008; 51: S98.
Lapsys NM, Layfield R, Baker E et al. Chromosomal location of the human transketolase gene. Cytogenet Cell Genet 1992; 61: 274–277.
Freedman BI, Bowden DW, Rich SS et al. Genome-wide linkage scans for renal function and albuminuria in type 2 diabetes mellitus: the Diabetes Heart Study. Diabet Med 2008; 25: 268–276.
Pacal L, Tomandl J, Tanhauserova V et al. Thiamine levels and transketolase genetic variants as modifiers of progression of diabetic nephropathy. Diabetologia 2009; 52: 1079.
Bakker SJL, Hoogeveen EK, Nijpels G et al. The association of dietary fibres with glucose is partly explained by concomitant intake of thiamine: the Hoorn study. Diabetologia 1998; 41: 1168–1175.
Wong CY, Qiuwaxi JA, Chen H et al. Daily intake of thiamine correlates with the circulating level of endothelial progenitor cells and the endothelial function in patients with type II diabetes. Mol Nutr Food Res 2008; 52: 1421–1427.
Arora S, Lidor A, Abularrage CJ et al. Thiamine (vitamin B1) improves endothelium-dependent vasodilatation in the presence of hyperglycemia. Ann Vasc Surg 2006; 20: 653–658.
Jerums G et al. Does Benfotiamine alter microalbuminia and hyperfiltration in patients with type 2 diabetes. In: The Maillard Reaction: Interface Between Aging, Nutrition and Metabolism (Thomas M and Forbes J eds.), in press.
Alkhalaf A, Klooster A, van Oeveren W et al. A Double-Blind, Randomized, Placebo-Controlled Clinical Trial on Benfotiamine Treatment in Patients with Diabetic Nephropathy. Diabetes Care 2010; 33: 1598-1601.
Acknowledgments
We thank Diabetes UK, Juvenile Diabetes Research Foundation, and the Pakistan Higher Education Commission for support for our thiamine-related research.
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Thornalley, P.J., Rabbani, N. (2011). Thiamine in Diabetic Renal Disease: Dietary Insufficiency, Renal Washout, Antistress Gene Response, Therapeutic Supplements, Risk Predictor, and Link to Genetic Susceptibility. In: Miyata, T., Eckardt, KU., Nangaku, M. (eds) Studies on Renal Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press. https://doi.org/10.1007/978-1-60761-857-7_5
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